Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK

Cynthia Mueller, Avery August

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, TH2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This TH2-type response suggests a prominent role for TH2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of TH2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK-/- mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the TH2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.

Original languageEnglish (US)
Pages (from-to)5056-5063
Number of pages8
JournalJournal of Immunology
Volume170
Issue number10
DOIs
StatePublished - May 15 2003

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Protein-Tyrosine Kinases
Asthma
Immunoglobulin E
Cytokines
Interleukin-13
Interleukin-5
Eosinophils
Anti-Asthmatic Agents
T-Lymphocytes
Lung
emt protein-tyrosine kinase
Allergens
Pneumonia
Pathology
Inflammation
Serum

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Mueller, Cynthia ; August, Avery. / Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK. In: Journal of Immunology. 2003 ; Vol. 170, No. 10. pp. 5056-5063.
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Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK. / Mueller, Cynthia; August, Avery.

In: Journal of Immunology, Vol. 170, No. 10, 15.05.2003, p. 5056-5063.

Research output: Contribution to journalArticle

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